Comparative Validation of the S-STS, the ISST-Plus, and the C-SSRS for Assessing the Suicidal Thinking and Behavior FDA 2012 Suicidality Categories.

OBJECTIVE: This exploratory study examines the concurrent validity for mapping symptoms of suicidal ideation, self-harm, and suicidal behavior as recorded on the InterSePT Scale for Suicidal Thinking-Plus, the Sheehan-Suicidality Tracking Scale (clinician- and patient-rated and reconciled patient/clinician versions), and the Columbia-Suicide Severity Rating Scale to the 11 United States Food and Drug Administration-Classification Algorithm of Suicide Assessment (September 2012) categories. METHOD: Forty subjects with varying degrees of suicidal ideation and behavior severity (from not present to extremely severe) were recruited from inpatient, outpatient, and emergency room settings. Each patient was interviewed using all three scales (InterSePT Scale for Suicidal Thinking-Plus, the Sheehan-Suicidality Tracking Scale, and the Columbia-Suicide Severity Rating Scale) on the same day. The scales were administered in a random sequence by three independent raters who were blind to the ratings on the other scales. RESULTS: The Sheehan-Suicidality Tracking Scale and the InterSePT Scale for Suicidal Thinking-Plus show acceptable agreement with the Columbia-Suicide Severity Rating Scale in detecting the presence or absence of the 2012 Food and Drug Administration-Classification Algorithm of Suicide Assessment categories 1, 5, 6, 10, and 11 (passive ideation; active ideation with method, intent, and plan; completed suicide; preparatory actions; and self-injurious behavior) but not of categories 2, 3, and 4 (3 other active suicidal ideation combination categories) or to 8 and 9 (aborted and interrupted attempt). Despite the significant disagreement between the Columbia-Suicide Severity Rating Scale on the one side and the InterSePT Scale for Suicidal Thinking-Plus and the Sheehan-Suicidality Tracking Scale on the other in the ability to accurately map to the 2012 Food and Drug Administration-Classification Algorithm of Suicide Assessment categories on some items, there was close agreement between the InterSePT Scale for Suicidal Thinking-Plus and the Sheehan-Suicidality Tracking Scale on these categories. CONCLUSION: The results of this exploratory study invite discussion and debate about the validity of the Columbia-Suicide Severity Rating Scale and its ability to accurately assess key active suicidal ideation categories, since it disagrees so much with the other two standardized scales that agree so closely with each other.

Simple Measures of Hopelessness and Impulsivity are Associated with Acute Suicidal Ideation and Attempts in Patients in Psychiatric Crisis.

OBJECTIVE: To explore the authors' predictions 1) that hopelessness would positively correlate with suicidal ideation and that impulsivity (either transient urges to self-harm or impulsive acting out) would positively correlate with suicidal behavior, and 2) that the recent or long-standing nature of the traits will have corresponding effects on reported histories of suicidal ideation and behavior. DESIGN: Questionnaire validation trial in which each subject received every measure in counterbalanced fashion. SETTING: Inpatient and outpatient psychiatric settings associated with a medium-sized medical school in the southeastern United States. PARTICIPANTS: Forty-five subjects presenting with varying levels of suicidal ideation and behavior completed measures providing information about their histories of suicidal ideation and behavior, recent feelings of hopelessness, feelings of general hopelessness, recent feelings of difficulty controlling urges to self-harm, and feeling about general levels of impulsivity. MEASUREMENTS: The InterSePT Scale for Suicidal Thinking-Plus, the Sheehan-Suicidality Tracking Scale, the Columbia-Suicide Severity Rating Scale, and six additional questions to assess hopelessness and impulsivity. RESULTS: Recent and trait hopelessness correlated positively with suicidal ideation. Patients who reported any suicide attempt endorsed higher levels of general impulsivity than those who did not report a history of at least one suicide attempt. Those enrolled in the study secondary to a very recent suicide attempt reported more difficulties with recent suicidal impulses. CONCLUSION: Simple measures of hopelessness and impulsivity are associated with suicidal ideation and attempts and may add to determination of suicide risk.

Delayed sleep timing and symptoms in adults with attention-deficit/hyperactivity disorder: a controlled actigraphy study.

Patients with attention-deficit/hyperactivity disorder (ADHD) often exhibit disrupted sleep and circadian rhythms. Determination of whether sleep disturbance and/or circadian disruption are differentially associated with symptom severity is necessary to guide development of future treatment strategies. Therefore, we measured sleep and ADHD symptoms in participants aged 19-65 who met the DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) criteria for ADHD and insomnia without psychiatric comorbidities by monitoring actigraphy and daily sleep logs for 2 wks, as well as the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), the ADHD Rating Scale (ADHD-RS), and a clinic-designed sleep behavior questionnaire. Principal components analysis identified correlated circadian- and sleep-related variables in all participants with ADHD who completed the study (n = 24). The identified components were entered into a backwards stepwise linear regression analysis, which indicated that delayed sleep timing and increased sleepiness (ESS) (but not sleep duration or sleep efficiency) significantly predicted greater severity of both hyperactive-impulsive and inattentive ADHD symptoms (p < .05 for partial regression coefficients). In addition, combined subtypes had the most impaired age-adjusted sleep quality (PSQI scores; p < .05 compared with healthy controls; n = 13), and 91.7% of them reported going to bed late due to being "not tired/too keyed up to sleep" compared with 57.2% and 50% of inattentive and symptom-controlled participants, respectively (p < .05). In conclusion, the results of this study suggest that ADHD symptom severity correlates with delayed sleep timing and daytime sleepiness, suggesting that treatment interventions aimed at advancing circadian phase may improve daytime sleepiness. In addition, ADHD adults with combined hyperactive-impulsive and inattentive symptoms have decreased sleep quality as well as the delayed sleep timing of predominately inattentive subtypes.

Efficacy of risperidone augmentation to antidepressants in the management of suicidality in major depressive disorder: a randomized, double-blind, placebo-controlled pilot study.

OBJECTIVE: Major depressive disorder (MDD) is a severe mental illness with high risk of suicidality. Antidepressant treatment alone is not sufficient for the acute management of risk-taking symptoms of depression. This pilot study was designed to investigate the efficacy of risperidone augmentation to antidepressants in the acute management of suicidality and other core symptoms in MDD with suicidality. METHOD: Twenty-four adult men and women diagnosed with MDD (DSM-IV), having a depressive episode with suicidality despite taking an antidepressant, were enrolled in an 8-week double-blind, placebo-controlled study. Subjects were randomly assigned to receive risperidone (0.25-2 mg/day) or placebo while continuing on their antidepressant therapy. Clinical efficacy in suicidality, depressive symptoms, and impulsivity were assessed after treatment with study drugs for 4 days, weekly for 4 weeks, then every other week for 4 weeks. Adverse events were also recorded at each visit. The study was conducted from June 2004 to April 2007. RESULTS: Risperidone significantly reduced suicidal ideations in MDD patients, and the overall effect of risperidone appeared to be superior to placebo. The effect of risperidone was rapid, with onset at 2 weeks' treatment, and was sustained along the course of 8 weeks' treatment. Furthermore, risperidone demonstrated superiority to placebo in improving other symptoms related to suicidality and having better trial completion rate, and the low dose risperidone was well tolerated by subjects in this study. CONCLUSION: Data from this pilot study suggest that risperidone is beneficial as an augmenting treatment in MDD patients who have developed high-risk suicidal ideation during a depressive episode. The antisuicidality effect of risperidone is especially valuable in the acute management of severe depressive symptoms. Although the pilot study is limited by small sample size, the promising results warrant further larger scale investigation in the efficacy of atypical antipsychotics in the treatment of severe depression with suicidality. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00167154.

Lithium regulates glycogen synthase kinase-3beta in human peripheral blood mononuclear cells: implication in the treatment of bipolar disorder.

BACKGROUND: Bipolar disorder has been linked to alterations in the multifunctional enzyme glycogen synthase kinase-3beta (GSK3beta). The mood stabilizer lithium inhibits GSK3beta in vitro and in mouse brain, and this is currently the strongest known potential therapeutic target of lithium. We tested whether lithium modified GSK3beta in vivo or in vitro in peripheral blood mononuclear cells (PBMCs) from healthy control and bipolar disorder subjects. METHODS: The PBMCs were obtained from 23 healthy control subjects, 9 bipolar subjects currently treated with lithium, and 13 lithium-free bipolar subjects. Immunoblot analyses were used to measure the inhibited, serine9-phosphorylated GSK3beta. RESULTS: The level of phospho-Ser9-GSK3beta in PBMCs was regulated by agents that modified kinases and phosphatases acting on GSK3beta and was increased by in vitro lithium treatment. More important, phospho-Ser9-GSK3beta levels were eightfold higher in PBMCs from lithium-treated bipolar than healthy control subjects. CONCLUSIONS: Signaling pathways regulating serine9-phosphorylation of GSK3beta can be studied in human PBMCs. Both in vitro and in vivo therapeutic lithium treatment is associated with a large increase in phospho-Ser9-GSK3beta in PBMCs. Therefore, the inhibitory serine9-phosphorylation of GSK3beta in human PBMCs may provide a biochemical marker to evaluate the association between GSK3beta inhibition and therapeutic responses to lithium treatment.

Risperidone and haloperidol augmentation of serotonin reuptake inhibitors in refractory obsessive-compulsive disorder: a crossover study.

BACKGROUND: Although serotonin reuptake inhibitors (SRIs) are the first-line treatment for obsessive-compulsive disorder (OCD), approximately half of patients with OCD do not respond adequately to SRI monotherapy. Patients with predominant obsessions are common in OCD and are often difficult to treat, necessitating adjunctive treatment. METHOD: This was a 9-week, double-blind, placebo-controlled, crossover study comparing the benefits of 2-week adjunctive treatments with risperidone, haloperidol, and placebo in patients with OCD (DSM-IV criteria) who continued to have severe symptoms despite taking a stable dose of an SRI. Eligible patients must have been receiving a therapeutic dose of an SRI for at least 12 weeks and at the screening visit had a score > or = 10 on items 1-5 (obsession) and a total score > or = 16 on the Yale-Brown Obsessive Compulsive Scale (YBOCS). Data were collected from January 1999 through April 2002. RESULTS: Sixteen patients were enrolled and 12 completed the study. On the YBOCS, both risperidone and haloperidol significantly reduced obsession (p < .05) when compared with placebo. There was a tendency that haloperidol, and to a lesser degree risperidone, also reduced the compulsion and the total YBOCS scores. These results were accompanied by a reduction in the Hopkins Symptom Checklist 90-revised (SCL-90R) anxiety scale score. According to the 17-item Hamilton Rating Scale for Depression, the SCL-90R depression scale, and the Profile of Mood States, risperidone, but not halo-peridol, also improved depressed mood. Neither risperidone nor haloperidol changed neurocogni-tive function during the 2-week treatment. All 12 patients completed the 2-week risperidone treatment, but 5 of the 12 terminated haloperidol treatment early owing to intolerable side effects. CONCLUSION: Adjunctive risperidone improved obsessions and depressed mood and was well tolerated in patients with SRI-refractory OCD.